期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 34, 期 7, 页码 1120-1121出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.34.1120
关键词
fibroblast growth factor 21; rosiglitazone; pioglitazone; bezafibrate; HepG2; mouse liver
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [22790237]
- Grants-in-Aid for Scientific Research [22790237] Funding Source: KAKEN
Fibroblast growth factor 21 (FGF21) is an effective metabolic regulator of glucose and lipid homeostasis in the context of insulin resistance, glucose intolerance and dyslipidemia in diabetic rodents and monkeys, and peroxisome proliferator-activated receptor alpha (PPAR alpha) directly induces FGF21 expression in the rodent liver. Recent findings suggest that the effects and regulation of FGF21 qualitatively differ between rodents and humans. Here, we examined the effects of PPAR alpha and PPAR gamma agonists on FGF21 mRNA expression in the mouse liver and in cultured hepatocytes. Intraperitoneal injection of both bezafibrate and pioglitazone induced FGF21 mRNA expression in the mouse liver. Rosiglitazone and pioglitazone as well as bezafibrate significantly induced FGF21 mRNA expression in cultured mouse hepatocytes. On the other hand, both rosiglitazone and pioglitazone significantly induced, whereas bezafibrate did not affect FGF21 mRNA expression in the human liver carcinoma cell line HepG2. Bezafibrate significantly induced pyruvate dehydrogenase kinase 4 mRNA expression, suggesting that HepG2 cells are sensitive to bezafibrate like the mouse liver. Our findings suggest that PPAR gamma-activating antidiabetic drugs such as rosiglitazone and pioglitazone induce FGF21 expression in mouse and human hepatocytes, and that PPAR gamma rather than PPAR alpha might play an important role in human FGF21 production.
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